Two GIMM-CARE projects, awarded today by the Gilead GÉNESE Program, aim to develop new therapies for breast cancer and brain metastases

The GIMM Foundation – Gulbenkian Institute for Molecular Medicine, through its translational research branch GIMM-CARE, is committed to finding solutions for breast cancer, a disease that affects one in eight women in Portugal.

This week, as part of this mission, two projects led by researchers Rita Cascão and Sandra Casimiro have been awarded funding from the Gilead GÉNESE Program. Rita Cascão’s project focuses on brain metastases, which are associated with a worse prognosis in breast cancer patients. Sandra Casimiro, on the other hand, is developing a project targeting primary and metastatic breast cancer, investigating a new therapeutic approach centered on a promising target that could enhance the effectiveness of standard treatment.

The incidence of breast cancer has been increasing, both in the general female population and in women under 50. Understanding the biology of this highly heterogeneous and complex disease is imperative. One signaling pathway identified as a promising therapeutic target, the RANK receptor pathway, has been extensively studied worldwide, including by Sandra Casimiro in the Translational Laboratory of GIMM-CARE, led by Luís Costa. While inhibition of this pathway has been shown to consistently reduce tumor aggressiveness and improve treatment efficacy, the current therapeutic approach has demonstrated limited effectiveness in breast cancer. Currently, an antibody therapy is used to block RANK ligand, the molecule that binds to the receptor and activates the pathway. However, in tumor cells, this pathway can be activated independently. Because the existing therapy does not address these cases, Sandra Casimiro proposes developing a nanotechnology-based system with an innovative concept, capable of inhibiting RANK and its downstream molecules specifically in tumor cells.

“This approach offers significant clinical potential, as it effectively disrupts pathway activity, reduces tumor aggressiveness, overcomes treatment resistance, and limits immune evasion in various breast cancer subtypes,” explains Sandra Casimiro. “The clinical application of this nanotechnology, whether in combination with existing therapies or as monotherapy, could benefit women across different stages of the disease, offering new hope in tackling this global health challenge.”

When asked about her motivation for studying breast cancer, Sandra Casimiro shares:

“It’s impossible to remain indifferent to the alarming rise in breast cancer cases and the devastating impact of this disease worldwide. As a woman and mother of a daughter, as well as a sister and aunt to other women, I naturally feel deeply concerned about this reality. As a scientist, I see this field as both an immense challenge and an opportunity. Breast cancer is extremely heterogeneous, and there are still many unanswered questions regarding its origin and biology. We need major improvements in early detection and the treatment of localized tumors.” She adds: “On the other hand, we know that cancer spread (metastasis) is the leading cause of mortality in breast cancer. In this context, early identification of metastases and the development of more effective treatments are crucial to transforming breast cancer into a manageable chronic disease. Scientific research is essential at every stage of the disease.”

It is precisely on metastasis, particularly brain metastasis, that the second Gilead GÉNESE award-winning project focuses. This project is led by Rita Cascão in the Translational Laboratory headed by Cláudia Faria.

Brain metastases are one of the leading causes of death in breast cancer patients, mainly due to the limited effectiveness of current treatments. Understanding the mechanisms behind brain metastasis is key to identifying new therapeutic targets. Cláudia Faria’s research team, where Rita Cascão will develop this project, has recently identified a protein that promotes the spread of cancer cells to the brain. Now, in this project, they will explore the hypothesis that this protein makes cancer cells better adapted to proliferate in the brain.

To investigate this, Rita Cascão aims to identify the cellular metabolism of brain metastases from breast cancer patients and analyze how this protein interacts with metabolic pathways. The goal is to find new therapeutic targets that could lead to more effective treatments for breast cancer brain metastases.

Having always been drawn to translational research, where clinical questions directly drive scientific investigation, Rita Cascão expresses her enthusiasm for the project:

“It’s fantastic to be part of projects that have the potential to make a significant impact on the treatment of difficult-to-treat diseases, such as brain metastases from breast cancer.”

Both awarded projects highlight a crucial aspect of GIMM-CARE’s mission: conducting research in close collaboration with clinicians and hospitals. Both Sandra Casimiro and Rita Cascão emphasize the importance of bringing scientists and physicians together to develop translational projects, a defining feature of GIMM-CARE’s approach.

Together, scientists and clinicians remain committed to finding solutions for emerging clinical challenges.